However, this property is unlikely to explain the lack of effect of risperidone on stress-induced anhedonia, as mianserin abolished this anhedonia and decreased selfstimulation behavior in nonstressed animals These variations in Epigenetic inhibitor supplier self-stimulation thresholds in nonstressed rats most, probably reflect, subtle motor and/or cognitive deficits induced by those

substances. Figure 5. Lack of effect of an antipsychotic (risperidone) on stress-induced anhedonia.26 Top: Variations of self-stimulation Inhibitors,research,lifescience,medical threshold in stressed rats treated with risperidone 0.3 mg/kg bid intraperitoneally (blue squares) or placebo (open circles) as a function … In summary, the results presented above have shown that the stress-induced anhedonia model is able to demonstrate the activity of electroshock and antidepressant drugs representing different, biochemical mechanisms of action, whereas an antipsychotic drug was inactive. In addition, other related studies Inhibitors,research,lifescience,medical have shown that treatment with a tranquilizer (chlordiazepoxide),an analgesic (morphine), neuroleptics (haloperidol,chlorprothixcnc), or a psycho stimulant

(amphetamine) also failed to reduce stressinduced anhedonia in rats.27,28 Therefore, the anhedonia model offers a fair degree of predictive validity. Inhibitors,research,lifescience,medical TMs simulation of depression should allow, on the one hand, to detect novel types of substances acting on depressed mood to be developed, and, on the other hand, the rapidity of onset of those medications to be predicted. Theoretical validity and aspect validity Evaluating the theoretical and aspect, validities of a simulation of depression consists in examining the degree of resemblance of the model with the syndrome it is supposed to reproduce. Ideally, an animal model Inhibitors,research,lifescience,medical should resemble the disease it, simulates with regard to its etiology, symptomatology, treatment, and biological basis. In addition, a heuristic animal model should exhibit, similarities with the core symptoms of a pathology rather Inhibitors,research,lifescience,medical than with the secondary symptoms. Anhedonia, a core symptom of depression As mentioned earlier, DSM-IV defines two core symptoms in the diagnosis of a depressive

episode: depressed mood (a subjective feeling impossible to simulate before in animals) and anhedonia. The choice of anhedonia as an essential characteristic of this model provides this simulation with a remarkable aspect validity. Moreover, this simulation exhibits other similarities with depression. First, it can show a curative effect, of antidepressant, treatment on hedonic deficit, and not, only a prophylactic effect. Second, the stress regimen continues during the treatment period, like the clinical situation, as there is usually no major change in the life conditions of a depressed patient that could be associated with treatment. Third, the time course of the antidepressant effect (10 to 20 days) in the anhedonia model corresponds to the time course observed clinically.